Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00054756
• Collaborator: (none)
• Enrollment: 96
• Location: 1
• Arm: 1
• Duration (Months): 139.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will determine the safety and activity of a new formulation of thyrotropin-releasing hormone (TRH), a drug used for diagnosing and evaluating patients with certain thyroid gland abnormalities. Normal thyroid gland function depends on proper chemical signaling between the thyroid gland, the hypothalamus (the part of the brain where TRH is made), and the pituitary (another part of the brain). The TRH test helps assess this interaction. Production of the only FDA-approved preparation of TRH was stopped in July 2002. As a result, to have a continuous source of TRH available for NIH clinical and research purposes, the NIH Clinical Center (CC) Pharmacy Department produced a pharmaceutical grade formulation of TRH for patient use. This study will test the CC formulation in healthy volunteers to show that its activity and side effects are similar to those of the previously available commercial test preparation. It will then be studied in CC patients for whom the diagnostic test is recommended.

Healthy volunteers between 18 and 65 years of age and all patients requiring TRH evaluation of hypothalamic-pituitary-thyroid gland interaction may be eligible for this study. Patients include those with pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre- and post-operative evaluation of pituitary tumors. Normal volunteers will be screened with a medical history, physical examination, and blood tests. Women of child-bearing potential will be given a pregnancy test; pregnant and breast-feeding women may not participate.

The TRH test procedure will be the same for healthy volunteers and patients. All participants fast from midnight before the morning of the test. In the morning, a catheter (flexible plastic tube) is inserted into an arm vein for easy injection of the TRH and collection of blood samples. Blood pressure is monitored before and during the test. A blood sample is drawn, and then TRH is given through the catheter over a 1-minute period. Another nine blood samples are collected over a 3-hour period from the time of the TRH injection for measuring levels of various hormones. A total of less than 4 tablespoons of blood is taken for the test.

Condition or Disease	Intervention/Treatment	Phase
Healthy; Pituitary Disease; Thyroid Disease	Drug: TRH (Thyrotropin Releasing Hormone)	Phase 2

Detailed Description

Thyrotropin releasing hormone (TRH) is a neuropeptide used in the diagnostic evaluation of patients with dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis. In healthy individuals, administration of TRH intravenously results in pituitary secretion of thyrotropin [thyroid-stimulating hormone (TSH)], which in turn stimulates the thyroid gland release of thyroid hormones; thyroxine (T4) and triiodothyronine (T3). TRH stimulates the secretion of other pituitary hormones under normal physiologic as well as pathologic conditions.

Under this protocol, TRH is used for routine diagnostic testing and research studies in adults and children. It is produced by the Pharmaceutical Development Section of the Clinical Center Pharmacy at the NIH. The safety, activity and comparability of this preparation were demonstrated in a small group of normal volunteers prior to its release for diagnostic and research use.

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Study of Thyrotropin Releasing Hormone in Patients With Thyroid or Pituitary Abnormalities
• Study Start Date: Feb 7, 2003
• Actual Primary Completion Date: Sep 26, 2014
• Actual Study Completion Date: Sep 26, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Thyrotropin Releasing Hormone Subjects receiving TRH (Thyrotropin Releasing Hormone)	Drug: TRH (Thyrotropin Releasing Hormone)

Outcome Measures

Primary Outcome Measures

1. TSH Response to TRH [180 minutes from infusion]

   Serum TSH Levels in Response to TRH Administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• DIAGNOSTIC STUDY PROTOCOL

Inclusion Criteria:

-All adults and children requiring dynamic testing of the hypothalamic-pituitary axis for the evaluation of pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre-and post-operative evaluation of pituitary adenomas (glycoprotein hormone secreting tumors, growth hormone secreting tumors and TSH secreting tumors).

Exclusion Criteria:

• Uncontrolled hypertension;

• Uncontrolled seizure disorder;

• Unstable coronary disease;

• Known allergy to TRH.

RESEARCH PROTOCOLS

-TRH is available for use in other IRB approved research protocols either using the standard diagnostic testing protocol or the modified TRH test.

Exclusion Criteria:

• Untreated hypertension;

• Coronary artery disease;

• History of asthma;

• History of seizures;

• Pregnancy;

• Known allergy to TRH.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Joanna Klubo-Gwiezdzinska, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Faglia G. The clinical impact of the thyrotropin-releasing hormone test. Thyroid. 1998 Oct;8(10):903-8. Review.
• Haigler ED Jr, Pittman JA Jr, Hershman JM, Baugh CM. Direct evaluation of pituitary thyrotopin reserve utilizing synthetic thyrotopin releasing hormone. J Clin Endocrinol Metab. 1971 Oct;33(4):573-81.
• Jackson IM. Thyrotropin-releasing hormone. N Engl J Med. 1982 Jan 21;306(3):145-55. Review.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT00054756
• Other Study ID Numbers: 030098; 03-DK-0098
• First Posted: Feb 10, 2003
• Last Update Posted: Aug 8, 2018
• Last Verified: Apr 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): Hypothalamic Releasing Factor; Neuropeptide; Diagnostic Testing; Pituitary Tumors; Central Hypothyroidism; Pituitary Disorder; Thyroid Disorder; Healthy Volunteer
• Additional relevant MeSH terms: Pituitary Diseases; Thyroid Diseases; Hormones; Thyrotropin-Releasing Hormone

Study Results

Participant Flow

Arm/Group Title	Thyrotropin Releasing Hormone
Arm/Group Description	Subjects receiving TRH (Thyrotropin Releasing Hormone)
Period Title: Overall Study
STARTED	96
COMPLETED	94
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Thyrotropin Releasing Hormone
Arm/Group Description	Subjects receiving TRH (Thyrotropin Releasing Hormone)
Overall Participants	96
Age (Count of Participants)
<=18 years	2 2.1%
Between 18 and 65 years	92 95.8%
>=65 years	2 2.1%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	38
Sex: Female, Male (Count of Participants)
Female	58 60.4%
Male	36 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.1%
Native Hawaiian or Other Pacific Islander	1 1%
Black or African American	19 19.8%
White	68 70.8%
More than one race	0 0%
Unknown or Not Reported	6 6.3%

Outcome Measures

1. Primary Outcome

Title	TSH Response to TRH
Description	Serum TSH Levels in Response to TRH Administration
Time Frame	180 minutes from infusion

Outcome Measure Data

Analysis Population Description

2 participants did not have results drawn at 180 minutes

Arm/Group Title	Thyrotropin Releasing Hormone
Arm/Group Description	Subjects receiving TRH (Thyrotropin Releasing Hormone)
Measure Participants	94
Mean (Full Range) [mcIU/mL]	11.47

Adverse Events

Time Frame	180 minutes after injection of TRH
Arm/Group Title	Thyrotropin Releasing Hormone
Arm/Group Description	Subjects receiving TRH (Thyrotropin Releasing Hormone)
All Cause Mortality
	Thyrotropin Releasing Hormone
	Affected / at Risk (%)	# Events
Total	0/96 (0%)
Serious Adverse Events
	Thyrotropin Releasing Hormone
	Affected / at Risk (%)	# Events
Total	0/96 (0%)
Other (Not Including Serious) Adverse Events
	Thyrotropin Releasing Hormone
	Affected / at Risk (%)	# Events
Total	0/96 (0%)

Limitations/Caveats

This study was conducted under an IND because the TRH was produced at NIH after the FDA approved manufacturer stopped producing the product. The intent of the study was to provide TRH for diagnostic purposes for patients at the NIH.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.